Recent studies have indicated that between a third and a half of all Americans are either overweight or obese (have a Body Mass Index (BMI) of greater than 25 kg/m2). Increases in caloric intake coupled with declines in exercise levels among the population have set the stage for a problem of epidemic proportions. The importance of addressing this problem and ultimately treating obesity is emphasized by the fact that this disease is either the underlying cause, or a risk factor, for developing diseases such as type II diabetes, congestive heart failure, osteoarthritis and sleep apnea among others.
Currently, the primary treatment for obesity typically involves behavioral change involving dietary restraints to reduce caloric intake coupled with aerobic and anaerobic exercise. Several dietary supplement drugs or other ingestible preparations are also used as appetite suppressors. In general, these techniques tend to produce only a temporary effect.
Recently, melanocortin receptors have been found to play a major role in the regulation of energy balance and obesity in humans as well as other mammals. In fact, weight loss has been found to result from the pharmacological stimulation of melanocortin system activity. In rodents pharmacological stimulation of certain melanocortin receptors has lead to decreased food intake, increased energy expenditure and weight loss (Pierroz et al., Diabetes 51: 1337-1345 (2002)). In humans intranasal administration of Alpha-melanocyte stimulating hormone (alpha-MSH), a 13 amino acid peptide hormone, in non-obese men resulted in decreased body weight due to the loss of fat mass. (Fehm et al., J. Clin. Endo. Metabol. 86: 1144-1148 (2001)).
To date, melanocortin receptor binding peptides such as alpha-MSH, have had limited use as pharmaceuticals due to their extremely short serum half-life. In addition, recent efforts to develop specific small molecule agonists of alpha-MSH have been slow; none of these compounds have advanced into the clinic.
Accordingly, a need exists for a more effective therapy for obesity and in particular more effective methods of delivering modulators of melanocortin system activity to subjects are needed.